Longitudinal studies of the association between peripheral CD27++ plasma cells and systemic lupus erythematosus disease activity: preliminary results

Boekel, Edwin ten; Prins, Meike C.; Vrielink, Gert-Jan; Kieviet, Wim de; Siegert, C. E. H.

doi:10.1136/ard.2010.133959

Cited by 6 publications

(9 citation statements)

References 9 publications

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“…HLA-DR lo plasmablasts are B cells that have recently become activated to differentiate, and are precursors to HLA-DR hi plasma cells, the abundance of which indicates active disease in patients 45 46. When compared with healthy controls, GILZ protein expression was significantly reduced in circulating HLA-DR lo plasmablasts in patients with SLE but was restored in patients treated with prednisolone (figure 1F), consistent with GILZ regulation by glucocorticoids in SLE in vivo as has been described in other contexts 47.…”

Section: Resultsmentioning

confidence: 99%

Glucocorticoid-induced leucine zipper (GILZ) inhibits B cell activation in systemic lupus erythematosus

et al. 2015

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Section: Resultsmentioning

confidence: 99%

Glucocorticoid-induced leucine zipper (GILZ) inhibits B cell activation in systemic lupus erythematosus

et al. 2015

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“…13 Interestingly, in contrast to adMS, PB—i.e., cells that are barely detectable in the periphery under normal conditions—turned out to be expanded overall in the pedMS cohort assessed here. Notably, heightened frequencies of circulating PB can also be detected in some prototypic, autoantibody-driven autoimmune disorders such as systemic lupus erythematosus (SLE) or neuromyelitis optica (NMO) 16,17 and are considered to be a biomarker for disease activity. 17 …”

Section: Discussionmentioning

confidence: 99%

“…Notably, heightened frequencies of circulating PB can also be detected in some prototypic, autoantibody-driven autoimmune disorders such as systemic lupus erythematosus (SLE) or neuromyelitis optica (NMO) 16,17 and are considered to be a biomarker for disease activity. 17 …”

Section: Discussionmentioning

confidence: 99%

B-cell populations discriminate between pediatric- and adult-onset multiple sclerosis

Schwarz

Balint

Korporal-Kuhnke

et al. 2017

Neurol Neuroimmunol Neuroinflamm

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Objective:To comparatively assess the B-cell composition in blood and CSF of patients with pediatric-onset multiple sclerosis (pedMS) and adult-onset multiple sclerosis (adMS).Methods:In this cross-sectional study, we obtained blood and CSF samples from 25 patients with pedMS (8–18 years) and 40 patients with adMS (23–65 years) and blood specimens from 66 controls (1–55 years). By using multicolor flow cytometry, we identified naive, transitional, isotype class-switched memory, nonswitched memory, and double-negative memory B-cell subsets as well as plasmablasts (PB) and terminally differentiated plasma cells (PC). Flow cytometric data were compared to concentrations of B-cell-specific cytokines in serum and CSF as determined by ELISA.Results:Frequencies of circulating naive B-cells decreased with higher age in controls but not in patients with multiple sclerosis (MS). B-cell patterns in CSF differed between pedMS and adMS with an acute relapse: in pedMS-derived CSF samples, high frequencies of nonswitched memory B cells and PB were present, whereas class-switched memory B cells and PC dominated in the CSF of patients with adMS. In pedMS, PB were also elevated in the periphery. Accumulation of PB in the CSF correlated with high intrathecal CXCL-13 levels and augmented intrathecal synthesis of immunoglobulin G and immunoglobulin M.Conclusions:We demonstrate distinct changes in intrathecal B-cell homeostasis in patients with pedMS during active disease, which differ from those in adults by an expansion of plasmablasts in blood and CSF and similarly occur in prototypic autoantibody-driven autoimmune disorders. This emphasizes the particular importance of activated B-lymphocyte subsets for disease progression in the earliest clinical stages of MS.

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“…Clinical evidence of plasmablast activity has been found in patients with NMO, 60 rheumatoid arthritis 30,61 and systemic lupus erythematosus 37,39,62,63 who receive the B-cell-depleting agent rituximab and are more likely to relapse early if their memory B cells, and more importantly their CD27 high plasmablasts, return earlier. In addition, mRNA from rheumatoid arthritis patients who are non-responsive to rituximab treatment demonstrate increases in mRNA markers of plasmablasts.…”

Section: Discussionmentioning

confidence: 99%

“…29 An abnormal expansion of CD27 high plasmablasts has been documented in the afflicted compartments of several autoimmune diseases, such as rheumatoid arthritis, 30 Sjogren’s, 31 systemic lupus erythematosus, 32 neuromyelitis optica (NMO), 33 ankylosing spondylitis 34 and pediatric ulcerative colitis. 35 In addition, patients with active systemic lupus erythematosus have greater counts of CD27 high plasmablasts in the periphery than in healthy controls (HCs) or patients with inactive disease, 32,36–39 suggesting these expanding plasmablasts may be contributing to damage associated with these autoimmune diseases.…”

Section: Introductionmentioning

confidence: 99%

Expansion of CD27high plasmablasts in transverse myelitis patients that utilize VH4 and JH6 genes and undergo extensive somatic hypermutation

et al. 2013

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Patients with the autoimmune disease multiple sclerosis (MS) typically present with the clinically isolated syndromes (CIS) transverse myelitis (TM) or optic neuritis (ON). B-cell disturbances have been well documented in patients with MS and CIS patients with ON, but not in CIS patients with TM, despite the fact that these patients have the worst clinical outcome of all CIS types. The goal of this study was to characterize the B-cell populations and immunoglobulin genetics in TM patients. We found a unique expansion of CD27high plasmablasts in both the cerebrospinal fluid and periphery of TM patients that is not present in ON patients. Additionally, plasmablasts from TM patients show evidence for positive selection with increased somatic hypermutation accumulation in VH4+ B cells and receptor editing that is not observed in ON patients. These characteristics unique to TM patients may impact disease severity and progression.

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Longitudinal studies of the association between peripheral CD27++ plasma cells and systemic lupus erythematosus disease activity: preliminary results

Cited by 6 publications

References 9 publications

Glucocorticoid-induced leucine zipper (GILZ) inhibits B cell activation in systemic lupus erythematosus

Glucocorticoid-induced leucine zipper (GILZ) inhibits B cell activation in systemic lupus erythematosus

B-cell populations discriminate between pediatric- and adult-onset multiple sclerosis

Expansion of CD27high plasmablasts in transverse myelitis patients that utilize VH4 and JH6 genes and undergo extensive somatic hypermutation

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